doi:10.1111/j.1440-1746.2011.06649.

GASTROENTEROLOGY

_6649

39..41

Functional dyspepsia, H. pylori and post infectious FD

Kwong Ming Fock
Department of Gastroenterology, Changi General Hospital, Singapore

Key words
functional dyspepsia, H. pylori, post infectious
FD.
Accepted for publication 24 January 2011.
Correspondence
Kwong Ming Fock, Department of
Gastroenterology, Changi General Hospital,
2 Simei Street 3, Singapore 529889. Email:
kwong_ming_fock@cgh.com.sg
Abbreviations and Standard Abbreviations
AGE: Acute Gastroenteritis, CI: Confidence
interval, EPS: Epigastric Pain Syndrome, FD:
Functional Dyspepsia, GDSS: Glasgow
Dyspepsia Severity Score, HP: H. pylori, IBS:
Irritable Bowel Syndrome, PDS: Postprandial
Distress Syndrome.

Abstract
Background: Functional Dyspepsia has been defined by Rome III as the presence of one
or more chronic dyspepsia symptoms in the absence of any organic, systemic, or metabolic
disease that is likely to explain the symptoms. Delayed gastric emptying, antral hypomotility and altered intestinal motility, decreased gastric accommodation, H.pylori infection,
enhanced visceral sensitivity, abnormal duodenal sensitivity to acid, carbohydrate maldigestion and psychological factors have all been identified in subgroups of patients with
functional dyspepsia.
Relationship between H.pylori, FD and post infectious FD: The relationship between
H. pylori infection and functional dyspepsia is controversial. H.pylori infection is present
in a minority of patients with FD. Symptoms and abnormalities of function such as gastric
emptying have not been consistently shown to be related to H.pylori infection. However,
meta-analysis has shown that H.pylori eradication therapy in FD results in a small but
statistically significant effect in H.pylori positive FD (relative risk reduction 10%). Guidelines for Helicobacter pylori infection have therefore strongly recommended H.pylori
eradication therapy in H.pylori positive FD patients. Post-infectious dyspepsia has been
described as a distinct clinical entity, based on a large retrospective study that showed a
subset of dyspeptic patients who had a history suggestive of post-infectious dyspepsia. In
a prospective study, investigators in Spain have found that development of dyspepsia was
increased fivefold at 1 year after acute Salmonella gastroenteritis. In post-infectious FD
patients, early satiety, weight loss, nausea, and vomiting are frequently reported together
with a higher prevalence of impaired gastric accommodation. More recently, infectious FD
has been found to be associated with persisting focal T-cell aggregates, decreased CD4+
cells and increased macrophage counts in the duodenum for several moths after acute
infection. This suggests impaired ability of the immune system to terminate the inflammatory response after acute insult.
Conclusion: In conclusion, H. pylori infections, as well as other gut infections, have been
associated with a subset of FD patients. Treatment of underlying infections can potentially
lead to improvement in this group of patients.

Introduction
Dyspepsia is a symptom complex that includes pain, discomfort
that is described as fullness or discomfort in the upper abdomen.
The symptom may result from a number of organic causes
such as peptic ulcer disease, gastro-oesophageal reflux disease,
pancreatico-biliary disease and malignancy. The majority of
patients with dyspepsia have no identifiable organic etiology for
their symptoms. Patients who have dyspeptic symptoms that are
not likely to be explained by organic, systemic or metabolic
disease are currently deemed to be suffering from functional dyspepsia (Rome III criteria) which was previously termed non-ulcer
dyspepsia or idiopathic dyspepsia.
An international panel of clinical investigators in 2006 classified functional dyspepsia into 2 subgroups: (1) Postprandial Distress Syndrome (PDS) and (2) Epigastric Pain Syndrome (EPS)
based on presence of one or more symptoms of epigastric pain,

epigastric burning, early satiation, or postprandial fullness

occurring for last 3 months and onset at least 6 months before
diagnosis. The Rome III consensus further stated that EPS and
PDS can overlap and heartburn can co-exist with these
syndromes.1
In their opinion, the committee considered the presence of H.
pylori infection as of uncertain clinical relevance in explaining the
symptoms. Hence H. pylori positive dyspeptics are included as
suffering from functional dyspepsia.

H. pylori and functional dyspepsia

The role of H. pylori in functional dyspepsia (FD) remains controversial. The prevalence rates of H. pylori associated gastritis in
FD has been variously reported to vary from 39% to 87% (Loffeld
1989, Tytgal 1993).

Journal of Gastroenterology and Hepatology 26 (2011) Suppl. 3; 3941

2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

39

Functional dyspepsia

KM Fock

Despite a number of investigations, no consistent differences in

the prevalence and severity of individual symptoms have been
detected in H. pylori positive versus H. pylori negative FD
subjects.2,3
Furthermore, no consistent association between gastric emptying rate, gastric accommodation and H. pylori infection have been
found. The only evidence that link H. pylori with FD is the
improvement of dyspepsia after H. pylori eradication in FD
patients. In a meta-analysis in 20084 that included 3566 patients
from 17 trials (with two from Asia), it was shown that there was a
10% relative risk reduction in the H. pylori eradication group (95%
CI = 6% to 14%) compared to placebo. The number needed to treat
to cure one case of dyspepsia was 14 (95% CI = 10 to 25). A
further three trials compared Bismuth based H. pylori eradication
with an alternative pharmacological agent and the results suggested that H. pylori eradication was more effective than either H2
receptor antagonists or sucralfate in treating FD. A randomized
double blind study showed that H. pylori eradication in FD
patients resulted in complete resolution of symptoms at 12 months
in 31% of patients versus 23.7% of patients treated with prokinetics and 63% of H. pylori treated patients reported improvement in
Glasgow Dyspepsia Severity Score (GDSS) versus 67% of
patients who received prokinetic therapy.5 Based on these data, the
Second Asia Pacific Consensus Guidelines for H. pylori infection
strongly recommended that H. pylori eradication is indicated for
H. pylori positive patients with investigated dyspepsia (Functional
Dyspepsia).6
To date, it has not been adequately explained why H. pylori
eradication led to resolution of dyspeptic symptoms in only a
minority of FD patients.

Post infectious functional dyspepsia

A post infectious origin has been suggested for some other functional bowel disorders such as irritable bowel syndrome (IBS). In
both retrospective and prospective studies, it is established that
IBS may follow an acute intestinal infection.7,8 the occurrence of
the gastroparesis syndrome after viral infection has also been
reported. No similar association has been reported for functional
dyspepsia until recently, Mearin reported9 a prospective cohort
study carried out in a Spanish village, Torroella de Mongr, where
an outbreak of acute gastroenteritis occurred. The study evaluated
the development of dyspepsia and IBS at 3, 6 and 12 months
following the acute gastroenteritis compared with randomly
selected controls. Prior to the acute gastroenteritis outbreak, the
prevalence of dyspepsia were similar in cases and controls (2.5%
vs 3.8%). Following the episode of acute gastroenteritis, the prevalence of dyspepsia increased significantly compared with unexposed subjects. At 1 year, 14% of the affected persons develop post
infectious dyspepsia. The relative risk for development of dyspepsia was 5.2 (95% CI = 2.7 to 9.8). There were some limitations to
this study as the response rate to the questionnaire at 12 month was
about 40%. Nevertheless, this study provided evidence to support
the concept of post infectious functional dyspepsia.
Earlier, in 2002, post infectious dyspepsia was recognised by
Tack and colleagues.10 In a large retrospective, tertiary center
study, they showed that a subset of dyspeptic patients with a
history suggestive of post infectious dyspepsia had more prevalent
symptoms of early satiety, weight loss, nausea and vomiting com40

pared with FD patients with unspecified onset dyspepsia. Furthermore, in patients with post infectious dyspepsia, there was a
significantly higher prevalence of impaired accommodation of the
proximal stomach but not in the prevalence delayed gastric emptying or hypersensitivity to gastric distension. This study not only
recognised post infectious dyspepsia but also the possible pathophysiology of post infectious dyspepsia.

Post infectious dyspepsia

and immunity
In post infectious IBS, persistent low grade colonic inflammation
and increased enterochromaffin cells (EC) and mast cells have
been found in rectal biopsies of patients.
Recently (2010), Li and colleagues11 reported that the number of
ECs in post infectious functional dyspepsia was significantly
higher than those in non-specific functional dyspepsia or in
healthy controls. The number of mast cells in post infectious
functional dyspepsia and non-specific functional dyspepsia in the
duodenum were significantly higher than in healthy controls.
Chemicals derived from mast cells and EC, including histamine,
tryptase and 5HT were also higher than in post infectious and
non-specific FD compared with healthy controls. These observations suggest impaired ability of the immune system to terminate
the inflammatory response after acute infection leading to release
of potent chemicals that may be involved in the pathogenesis of
post infectious functional dyspepsia.
In addition, focal T cell aggregates, decreased CD4+ cells and
increased macrophage counts have been observed in the duodenum of patients with presumed post-infectious FD lending
support to the notion that immunity has a role in post infectious
FD.12
It is conceivable that H. pylori infection influences duodenal
immune cells in a similar fashion. In fact, the number of duodenal
intraepithelial lymphocytes is significantly increased in H. pylori
positive FD patients compared with H. pylori negative FD
patients.13
H. pylori colonisation on the gastric mucosa enhances inflammatory cell infiltration which may persist in some individuals after
the eradication of H. pylori. Whether H. pylori infection could
contribute to immune activation observed in the duodenal mucosa
of H. pylori positive FD patients should be further investigated and
could explain why H. pylori eradication does not always lead to
resolution of dyspeptic symptoms.

Conclusion
In conclusion, FD is a heterogeneous disorder that is characterised
by the presence of recurrent or persistent symptoms thought to
originate in the gastroduodenal region without any organic, systemic or metabolic disease that is likely to explain the symptoms.
The pathophysiology of FD is multifactorial. Gastrointestinal
infection has been recently recognised as a possible aetiological
factor in the pathogenesis of FD. Although the role of H. pylori in
FD has been mired in controversy, it is plausible that immune
mechanisms seen in other gut infection could be similarly involved
in and lead to symptoms of dyspepsia.

Journal of Gastroenterology and Hepatology 26 (2011) Suppl. 3; 3941

2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

KM Fock

Functional dyspepsia

References
1 Tack J, Talley NJ, Camilleri M et al. Functional gastroduodenal
disorders. Gastroenterology 2006; 130: 146679.
2 Saslow SB, Thumshirn M, Camilleri M et al. Influence of H. pylori
infection on gastric motor and sensory function in asymptomatic
volunteers. Dig. Dis. Sci. 1998; 43: 25864.
3 Tucci A, Corinaldesi R, Stanghellini V et al. Helicobacter pylori
infection and gastric function in patients with chronic idiopathic
dyspepsia. Gastroenterology 1992; 103: 76874.
4 Moayyedi P, Soo S, Deeks J et al. Eradication of helicobacter pylori
for non-ulcer dyspepsia. Cochrane Database Syst. Rev. 2008; (2):
CD 002096.
5 Ang TL, Fock KM, Teo EK et al. Helicobacter pylori eradication
versus prokinetics in the treatment of functional dyspepsia: a
randomized, double-blind study. J. Gastroenterol. 2006; 41: 64753.
6 Fock KM, Katelaris P, Sugano K et al. Second AsiaPacific
consensus guidelines for helicobacter pylori infection. J.
Gastroenterol. Hepatol. 2009; 24: 1587600.
7 Spiller RC, Jenkins D, Thornley JP et al. Increased rectal mucosal
enteroendocrine cells, T lymphocytes, and increased gut permeability

10

11

12

13

following acutecampylobacter enteritis and in post-dysenteric

irritable bowel syndrome. Gut 2000; 47: 80411.
Gwee KA, Read NW, Graham JC et al. Psychometric scores and
persistence of irritable bowel after infectious diarrhoea. Lancet 1996;
347: 1503.
Mearin F, PrezOliveras M, Perell A et al. Dyspepsia and irritable
bowel syndrome after a salmonella gastroenteritis outbreak: one-year
follow-up cohort study. Gastroenterology 2005; 129: 98104.
Tack J, Demedts I, Dehondt G et al. Clinical and pathophysiological
characteristics of acute-onset functional dyspepsia. Gastroenterology
2002; 122: 173847.
Li X, Chen HM, Lu H et al. The study on the role of inflammatory
cells and mediators in post-infectious functional dyspepsia. Scand. J.
Gastroenterol. 2010; 45: 57381.
Kindt S, Tertychnyy A, De Hertogh G et al. Intestinal immune
activation in presumed post-infectious functional dyspepsia.
Neurogastroenterol. Motil. 2009; 21: 832e56.
Gargala G, Lecleire S, Francois A et al. Duodenal intraepithelial T
lymphocytes in patients with functional dyspepsia. World J.
Gastroenterol. 2007; 13: 23338.

Journal of Gastroenterology and Hepatology 26 (2011) Suppl. 3; 3941

2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

41

Copyright of Journal of Gastroenterology & Hepatology is the property of Wiley-Blackwell and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.